Modulation of sensory neuron excitability by functionally altered NaV1.9 channels

Project: DFG ProjectsDFG Individual Projects

Project Details

Description

Voltage-gated sodium channels (NaV channels) are essential for the electrical signaling of nociceptive afferents because they trigger action potentials which transmit nociceptive information to the central nervous system. Consequently, gene mutations affecting the functions of NaV channels are associated with a whole spectrum of pain disorders. For example, an increase in the activity of NaV1.7 and NaV1.8 channels is known to cause severe neuropathic pain phenotypes, whereas the complete loss of functional NaV1.7 channels is associated with congenital analgesia. However, C-fiber-specific NaV1.9 channels seem to be unique among the group of nociceptor-specific NaV isoforms because gain-of-function variants of NaV1.9 were recently associated not only with neuropathic pain conditions, but – paradoxically – also with congenital analgesia. Although intensively discussed, the mechanisms underlying the opposing phenotypes, have thus far not been precisely defined. This project aims to identify cellular as well as molecular mechanisms underlying the opposing NaV1.9-dependent phenotypes congenital analgesia and neuropathic pain. A combination of molecular biology and electrophysiological methods will be employed to study the impact of disease-causing NaV1.9 variants on the electrical activity of sensory neurons and to identify functional alterations of NaV1.9 channels associated specifically with either analgesia or neuropathic pain conditions.
StatusActive
Effective start/end date01.01.14 → …

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

  • 201-01 Biochemistry
  • 205-04 Physiology

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